一例2N型遗传性血管性血友病家系的表型诊断和基因型分析

doi:10.16150/j.1671-2870.2018.02.006

诊断学理论与实践 ›› 2018, Vol. 17 ›› Issue (02): 151-154.doi: 10.16150/j.1671-2870.2018.02.006

一例2N型遗传性血管性血友病家系的表型诊断和基因型分析

金佩佩¹, 梁茜², 戴菁², 丁秋兰², 孙顺昌¹, 王学锋²

1.上海交通大学医学院附属瑞金医院北院检验科,上海 201801;
2.上海交通大学医学院附属瑞金医院检验科,上海 200025

收稿日期:2018-03-26 出版日期:2018-04-25 发布日期:2018-04-25
通讯作者: 王学锋 E-mail: wangxuefeng6336@Hotmail.com
基金资助:
国家自然基金青年科学基金（81601823）; 上海市科委自然科学基金（16ZR1422100）

Phenotype and genotype analysis of a Chinese pedigree with 2N type von Willebrand disease

JIN Peipei¹, LIANG Qian², DAI Jing², DING Qiulan², SUN Shunchang¹, WANG Xuefeng²

1. Department of Clinical Laboratory, Ruijin North Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China;
2. Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2018-03-26 Online:2018-04-25 Published:2018-04-25

摘要/Abstract

摘要： 目的：探讨1个遗传性血管性血友病（von Willebrand disease,vWD）2N型家系的表型诊断和基因型分析结果,明确患者的发病机制。方法：对该家系的先证者和家系成员进行出血时间、活化部分凝血活酶时间、瑞斯托霉素诱导的血小板聚集（ristocetin induced platelet aggregation,RIPA）试验、血管性血友病因子（von Willebrand factor,vWF）瑞斯托霉素辅因子、vWF抗原、vWF活性测定、vWF胶原结合试验、凝血因子Ⅷ（coagulation factor Ⅷ,FⅧ）活性、vWF与FⅧ结合试验检测,并作出表型诊断。提取先证者的外周血基因组DNA,用PCR法扩增VWF基因和F8基因的所有外显子及侧翼序列,通过直接测序分析VWF基因和F8基因变异。结果：vWD家系先证者的活化部分凝血活酶时间和出血时间明显延长,血浆瑞RIPA试验、vWF瑞斯托霉素辅因子、vWF抗原、vWF活性和vWF胶原结合试验检测结果均正常,FⅧ活性下降,vWF与FⅧ的结合能力降低。对先证者进行基因测序,发现其VWF基因19号外显子存在c.2446C>T（p.Arg816Trp）错义突变,其儿子在该位点为杂合突变,而先证者及家系成员的F8基因未发现突变。结论：c.2446C>T（p.Arg816Trp）错义突变是导致该家系先证者发生2N型遗传性vWD的原因。

关键词: 血管性血友病, 血管性血友病因子, 基因突变

Abstract: Objective: To analyze the phenotype and genotype of one Chinese pedigrees with von Willebrand disease and to investigate the molecular pathogenesis of the disease. Methods: Indices including bleeding time(BT), activated partial thromboplastin time (APTT), ristocetin-induced platelet aggregation(RIPA), von Willebarand factor-ristocetin cofactor (vWF:Rco), von Willebrand factor antigen (vWF:Ag), von Willebrand factor activity (vWF:Act), von Willebrand factor collagen binding assay (vWF:CB) and von Willebrand factor FⅧ binding assay (vWF: FⅧ:B) were detected for phenotype diagnosis. Peripheral blood DNA was extracted, and all of the exons and exon-intron boundaries of the VWF and F8 gene were amplified by polymerase chain reaction (PCR) and analyzed with direct sequencing. Results: The results revealed that APTT and BT of proband were prolonged while plasma RIPA, vWF:Rco, vWF:Ag, vWF:Act and vWF:CB were normal. FⅧ:C and vWF: FⅧ:B were significantly decreased. Homozygous missense mutation c.2446C>T (p.Arg816Trp) in exon 19 of VWF gene was identified in proband and heterozygous mutation was identified in his son. No mutation in F8 gene was found in proband. Conclusions: Homozygous missense mutation c.2446C>T (p.Arg816Trp) in exon 19 of VWF gene is the cause of 2N type von Willebrand disease in the proband.

Key words: von Willebrand disease, von Willebrand factor, Gene mutation

中图分类号:

R554⁺.1

金佩佩, 梁茜, 戴菁, 丁秋兰, 孙顺昌, 王学锋. 一例2N型遗传性血管性血友病家系的表型诊断和基因型分析[J]. 诊断学理论与实践, 2018, 17(02): 151-154.

JIN Peipei, LIANG Qian, DAI Jing, DING Qiulan, SUN Shunchang, WANG Xuefeng. Phenotype and genotype analysis of a Chinese pedigree with 2N type von Willebrand disease[J]. Journal of Diagnostics Concepts & Practice, 2018, 17(02): 151-154.

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一例2N型遗传性血管性血友病家系的表型诊断和基因型分析

Phenotype and genotype analysis of a Chinese pedigree with 2N type von Willebrand disease

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